title: Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy.
abstract: Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The ganglionic (alpha3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic and enteric autonomic ganglia. Autonomic ganglia are an important site of neural integration and regulation of autonomic reflexes. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Ganglionic AChR antibodies are found in many patients with autoimmune autonomic ganglionopathy (AAG). These antibodies recognize the alpha3 subunit of the ganglionic AChR, and thus do not bind non-specifically to other nicotinic AChR. Patients with high levels of ganglionic AChR antibodies typically present with rapid onset of severe autonomic failure, with orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia gravis, AAG is an antibody-mediated neurological disorder. Antibodies from patients with AAG inhibit ganglionic AChR currents and impair transmission in autonomic ganglia. An animal model of AAG in the rabbit recapitulates the important clinical features of the human disease and provides additional evidence that AAG is an antibody-mediated disorder caused by impairment of synaptic transmission in autonomic ganglia.
authors.affiliation: Department of Neurology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9036, USA. steven.vernino@utsouthwestern.edu
authors.forename: Steven
authors.initials: S
authors.lastname: Vernino
authors.forename: Steve
authors.initials: S
authors.lastname: Hopkins
authors.forename: Zhengbei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005725:Ganglia, Autonomic / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology; D020721:Nervous System Autoimmune Disease, Experimental / Q000276:immunology; D020361:Paraneoplastic Syndromes, Nervous System / Q000276:immunology; D054969:Primary Dysautonomias / Q000175:diagnosis / Q000276:immunology*; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000276:immunology* / Q000502:physiology; D012680:Sensitivity and Specificity; D009435:Synaptic Transmission; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D011978:Receptors, Nicotinic